title: Targeting receptor tyrosine kinases in  HER2-negative breast cancer.
abstract: OBJECTIVE
  The targeting of receptor tyrosine kinases (RTKs) has been a major area for breast cancer therapy, exemplified by the targeting of HER2-amplified breast cancer.
  
  
  RESULTS
  We review the data on the activation of RTKs in HER2-negative breast cancer, and discuss the clinical translational challenge of identifying cancers that are reliant on a specific kinase for growth and survival. Substantial evidence suggests that subsets of breast cancer may be reliant on specific kinases, and that this could be exploited therapeutically. The heterogeneity of breast cancer, however, and the potential for adaptive switching between RTKs after inhibition of a single RTK, present challenges to targeting individual RTKs in the clinic
  
  
  CONCLUSIONS
  Targeting of RTKs in HER2-negative breast cancer presents a major therapeutic opportunity in breast cancer, although robust selection strategies will be required to identify cancers with activation of specific RTKs if this potential is to be realized.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Anandappa
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Turner
mesh_terms: D000077384:Anastrozole; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000201:enzymology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D009570:Nitriles / Q000627:therapeutic use; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D020893:Receptor, ErbB-3 / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use; D015854:Up-Regulation
chemical_list: D000077384:Anastrozole; D066246:ErbB Receptors; D000077156:Gefitinib; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D014230:Triazoles; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human